PROJECT SUMMARY This project aims to expand the resources available for cross-national research on the epidemiology of Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). While cognitive impairment and dementia impose enormous burdens on families and governments around the world, and research is ongoing in many places, there are relatively few well-harmonized studies that allow good comparative or integrative analysis to exploit cross-national differences in determinants and outcomes of dementia. The Health and Retirement Study (HRS) family of international longitudinal studies of aging are closely harmonized on many dimensions of measurement and committed to public sharing of data to encourage research. The Harmonized Cognitive Assessment Protocol (HCAP) was developed to provide a common strong foundation to achieve more comparable assessments of impairment and dementia within this network and better harmonization to studies outside it. The HCAP has already been conducted with over 3,400 US participants in the HRS and with over 1,200 participants in the English Longitudinal Study of Ageing (ELSA). This project will add an additional 1,400 participants from the Irish Longitudinal Study of Ageing (TILDA) in the Republic of Ireland and 1,000 participants from the Northern Ireland Cohort Longitudinal Study of Ageing (NICOLA). All four studies have genomic data available to support research. As stand-alone cohorts these studies will support estimates of the prevalence of dementia and cognitive impairment in each nation and create the opportunity for future longitudinal follow-up to measure incidence rates. In conjunction with the larger samples of the parent studies they can be used to create harmonized measures of cognitive status on an even larger scale to support epidemiologic research on the full samples. Northern Ireland and the Republic share many genetic and environmental factors but the North experienced unique stress due to political violence. We will study its impact on DNA methylation and on rates of cognitive impairment and dementia. With their close association to clinical care, the Irish studies will undertake a valuable validation of the HCAP protocol against clinical diagnoses. The Irish studies bring uniquely valuable measures of cardiovascular health that can be studied for its association with dementia, including neurocardiovascular instability that is a key risk factor for falls. They also have retinal imaging that can detect cerebral microvascular disease, and detailed nutritional assessments not generally available in population-representative studies in the US.